3,4-Dicholoroaniline acute toxicity in male Fischer 344 rats.
The aromatic amine, 3,4-dichloroaniline (DCA) is an important intermediate in the chemical production of agricultural chemicals. A previous study had shown that nephrotoxicity was apparent 48 h after injection of 3,4-DCA. The purpose of this study was to examine the potential for 3,4-DCA to be toxic to the kidney, liver and urinary bladder 24 h after acute administration. Male Fischer 344 (F344) rats were injected (intraperitoneal (i.p.)) with 0.4, 0.8 or 1.0 mmol/kg 3,4-DCA hydrochloride (HCl) salt (2.5 ml/kg, 25% ethanol). Nephrotoxicity was apparent within 24 h in the 0.8 and 1.0 mmol/kg 3,4-DCA treated group and was characterized by elevated (P < 0.05) blood urea nitrogen (BUN) and kidney weight. Renal cortical slice accumulation ofp-aminohippurate (PAH) was also decreased in the 0.8 and 1.0 mmol/kg 3,4-DCA treated group relative to pair fed controls (PFC). Cellular changes were noted in the liver and bladder 24 h after 3,4-DCA administration. Plasma alanine transaminase (ALT) activity was elevated (P < 0.05) above PFC values 24 h after treatment with 0.8 or 1.0 mmol/kg indicating liver damage was apparent within 24 h. Morphological damage was apparent along the centrilobular region. Hematuria was observed in the 0.8 and 1.0 mmol/kg 3,4-DCA treated groups. Infiltration of erythrocytes and polymorphonuclear leukocytes was apparent within the urinary bladder upon examination by light microscopy. These results indicated that 3,4-DCA was toxic within 24 h and that the target tissues were the kidney, liver and urinary bladder. In vitro studies were conducted to compare the toxicity of two forms of 3,4-DCA, the free base and hydrochloride salt to determine whether chemical form contributes to renal cortical slice toxicity. Lactate dehydrogenase (LDH) release was elevated above control by 120 min exposure to 2 mM 3,4-DCA free base or hydrochloride salt. Pyruvate directed gluconeogenesis in renal slices was decreased relative to control by 0.5 mM 3,4-DCA free base and hydrochloride salt. The results from the in vitro studies indicates that the chemical form did not modify in vitro renal cortical slice toxicity.
Valentovic
M A
MA
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25704-9388, USA. valentov@marshall.edu
Yahia
T
T
Ball
J G
JG
Hong
S K
SK
Brown
P I
PI
Rankin
G O
GO
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology
D000814:Aniline Compounds; C014464:3,4-dichloroaniline; D000410:Alanine Transaminase